The overall goal of this proposal is to better understand the functional relevance and development of antigen-specific CD4+ T cell responses in the mouse model of influenza. The ability to potentiate and manipulate CD4+ T cell responses has important implications for immune therapy in infectious diseases, cancer and AIDS. In this study, influenza viruses containing defined CD4+ epitopes on the 1-Ab background inserted in either the hemagglutinin or neuraminadase will be generated using reverse genetics. These viruses will then be used to characterize the development, kinetics, phenotype and effector function of antigen-specific CD4 T cells in primary, secondary and memory phases of the C57BL/6 model of influenza infection using tetramer staining, intracellular cytokine staining and ELISPOT analyses. These data will be used to determine the effector mechanisms of antigen-specific CD4+ T cells in the influenza model. Using a transgenic T cell receptor mouse, the effect of the quantity and quality of CD4+ T cell responses on influenza primary and secondary infection will also be determined. Finally, the effects of antigen-specific vs. unrelated antigen priming by influenza on allergic responses on different genetic backgrounds will be examined.